The tracheobronchial mucus blanket provides an important barrier protecting airways epithelial cells against inhaled infectious agents and irritant gases and particles. In a number of chronic airway diseases, such as chronic bronchitis, the control of mucus production by submucosal gland cells and goblet cells is altered. The ensuing overproduction and hypersecretion of mucin glycoproteins can contribute directly to airway obstruction, airway plugging, and harboring bacterial infection. Recently, epidemiological studies have demonstrated that increases in morbidity and mortality, with underlying respiratory causes, are associated with exposure to ambient air particulate matter (PM) in many regions of the U.S. These increases in adverse health effects include a strong association between the incidence of chronic bronchitis and ambient PM. The biological plausibility of the association between PM and the increases in adverse respiratory health effects has been questioned because these effects have been observed at very low PM concentrations. By using an animal model of chronic bronchitis, the proposed studies will examine the hypothesis that ambient PM induces mucus hyperproduction and hypersecretion by altering the response to inhaled microbes. These studies will generate data establishing mechanistic links between PM and the worsening of already compromised physiological process. To determine the physiological pathways by which ambient PM can alter mucus production healthy animals and animals with compromised health will be exposed to concentrate ambient PM can alter mucus production, healthy animals and animals with compromised health will be exposed to concentrated ambient PM for controlled laboratory exposure of animals in this research project. The specific aim of this research proposal is stated below as the hypothesis which will be tested.